Vasopressin secretion in progressive autonomic failure: evidence for defective afferent cardiovascular pathways

Patients with progressive autonomic failure with multiple system atrophy show a severely blunted response of plasma arginine vasopressin to the stimulus of head-up tilt. Whether this could be due to lesions either at one or more sites within ascending neural pathways from cardiovascular stretch receptors in the thorax or, alternatively, to lesions affecting vasopressin secreting cells within the hypothalamus was investigated. The arginine vasopressin response to an intravenous infusion of hypertonic saline was determined in six patients with progressive autonomic failure. The mean plasma concentration of arginine vasopressin rose from 1.0 to 3.7 pmol/l, a change comparable to that observed in normal controls. This demonstrates normal functioning of the efferent connections from the osmoreceptors within the hypothalamus and suggests that the loss of vasopressin response to head-up tilt is due to lesions in ascending pathways from cardiovascular receptors. There was a significant rise in mean blood pressure during the infusions on patients with progressive autonomic failure, a change which was not observed with the controls. This may have been at least partly caused by the rise in circulating arginine vasopressin concentrations, since these patients have been reported to be extremely sensitive to the pressor effects of arginine vasopressin.